Unexpected elevation in valproic acid concentration and agranulocytosis in a patient with short-chain acyl-CoA dehydrogenase deficiency.
ACADS gene
Beta-oxidation
Neutropenia
Pharmacokinetics
Short-chain acyl-CoA dehydrogenase
Valproate sodium
West syndrome
Journal
Brain & development
ISSN: 1872-7131
Titre abrégé: Brain Dev
Pays: Netherlands
ID NLM: 7909235
Informations de publication
Date de publication:
May 2021
May 2021
Historique:
received:
17
10
2020
revised:
05
01
2021
accepted:
17
01
2021
pubmed:
8
2
2021
medline:
14
1
2022
entrez:
7
2
2021
Statut:
ppublish
Résumé
Short-chain acyl-CoA dehydrogenase (SCAD) deficiency is an autosomal recessive metabolic disorder or condition of fatty acid β-oxidation, caused by mutations in the gene encoding SCAD (ACADS). We report an infant with SCAD deficiency who unexpectedly exhibited an extremely high blood concentration of valproic acid (VPA) and agranulocytosis. An 8-month-old girl was diagnosed with West syndrome (infantile spasms), and VPA was administered at the standard level of 25 mg/kg/day. However, the blood concentration of VPA rose unexpectedly to 230 µg/mL (two- to three-fold higher than the expected value), and continued to remain relatively high even after the dosage was reduced (7 mg/kg/day, blood concentration of 88 µg/mL). Furthermore, she presented with a high-grade fever with agranulocytosis (neutrophil 231/µL). The abnormal pharmacokinetics and toxicity of VPA raised the suspicion of possible inborn errors of metabolism in the fatty acid β-oxidation pathway. Blood tandem mass spectrometry revealed a transient elevation of C4, and urine gas chromatography-mass spectrometry revealed a continuous elevation of ethylmalonate. Finally, gene analysis revealed compound heterozygous mutations, c.625G > A (p.G209S) and c.1031A > G (p.E344G), in ACADS. VPA should be avoided if a patient is suspected to have inborn errors of β-oxidation including SCAD deficiency.
Sections du résumé
BACKGROUND
BACKGROUND
Short-chain acyl-CoA dehydrogenase (SCAD) deficiency is an autosomal recessive metabolic disorder or condition of fatty acid β-oxidation, caused by mutations in the gene encoding SCAD (ACADS). We report an infant with SCAD deficiency who unexpectedly exhibited an extremely high blood concentration of valproic acid (VPA) and agranulocytosis.
CASE REPORT
METHODS
An 8-month-old girl was diagnosed with West syndrome (infantile spasms), and VPA was administered at the standard level of 25 mg/kg/day. However, the blood concentration of VPA rose unexpectedly to 230 µg/mL (two- to three-fold higher than the expected value), and continued to remain relatively high even after the dosage was reduced (7 mg/kg/day, blood concentration of 88 µg/mL). Furthermore, she presented with a high-grade fever with agranulocytosis (neutrophil 231/µL). The abnormal pharmacokinetics and toxicity of VPA raised the suspicion of possible inborn errors of metabolism in the fatty acid β-oxidation pathway. Blood tandem mass spectrometry revealed a transient elevation of C4, and urine gas chromatography-mass spectrometry revealed a continuous elevation of ethylmalonate. Finally, gene analysis revealed compound heterozygous mutations, c.625G > A (p.G209S) and c.1031A > G (p.E344G), in ACADS.
CONCLUSION
CONCLUSIONS
VPA should be avoided if a patient is suspected to have inborn errors of β-oxidation including SCAD deficiency.
Identifiants
pubmed: 33549404
pii: S0387-7604(21)00001-2
doi: 10.1016/j.braindev.2021.01.001
pii:
doi:
Substances chimiques
Anticonvulsants
0
Valproic Acid
614OI1Z5WI
Acyl-CoA Dehydrogenase
EC 1.3.8.7
Types de publication
Case Reports
Langues
eng
Sous-ensembles de citation
IM
Pagination
657-660Informations de copyright
Copyright © 2021 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.